Liposomes consist of at least one lipid bilayer membrane enclosing an aqueous internal compartment. Liposomes may be characterized by membrane type and by size. Small unilamellar vesicles (SUVs) have a single membrane and typically range between 0.02 and 0.05 .mu.m in diameter; large unilamellar vesicles (LUVs) are typically larger 0.05 .mu.m. oligolamellar large vesicles and multilamellar large vesicles have multiple, usually concentric, membrane layers and are typically larger than 0.1 .mu.m. Liposomes with several nonconcentric membranes, i.e., several smaller vesicles contained within a larger vesicle, are termed multivesicular vesicles.
Conventional liposomes are formulated to carry drugs or other active agents either contained within the aqueous interior space (water-soluble drugs) or partitioned into the lipid bilayer (water-insoluble drugs). As used herein, active agents "entrapped" within liposomes are those which are in the interior space of the liposome, compared to those which are partitioned into the lipid bilayer and contained within the vesicle membrane itself. Active agents which have short half-lives in the bloodstream are particularly suited to delivery via liposomes. Many anti-neoplastic agents, for example, are known to have a short half-life in the bloodstream such that their parenteral use is not feasible. However, the use of liposomes for site-specific delivery of active agents via the bloodstream is severely limited by the rapid clearance of liposomes from the blood by cells of the reticuloendothelial system (RES).
It is accordingly desirable to devise liposome formulations capable of delivering therapeutic amounts of active agent via parenteral administration, and resulting in an extended half-life of active agent in the blood stream.